8:46 PM
Sep 28, 2018
 |  BioCentury  |  Product Development

Deferred differentiation in migraine

How the anti-CGRP reimbursement landscape could shape in the near and long term

The best hope for CGRP antagonists to differentiate themselves lies in data that aren’t yet available. In the meantime, the makers of the migraine therapies will likely have to trade discounts on their already reasonable prices for favorable formulary status.

After decades of little progress in treating migraines, and only a handful of repurposed drugs to prevent it, on May 17, Amgen Inc.’s Aimovig erenumab-aooe became the first drug ever approved that was expressly developed to prevent the condition.

Its lone status was short lived, with two other drugs acting via the same mechanism approved in September, and a fourth likely by early 2020, setting up a showdown between four highly similar agents that will likely boil down to which company negotiates best with the payers.

Aimovig targets the calcitonin gene-related peptide (CGRP) receptor. Its competitors target the ligand. All four are mAbs.

Teva Pharmaceutical Industries Ltd.’s Ajovy fremanezumab-vfrm was approved by FDA on Sept. 14; Eli Lilly and Co.’s Emgality galcanezumab-gnlm was approved on Sept. 27. All three products are indicated for the preventive treatment of migraine in adults.

Alder Biopharmaceuticals Inc. plans to submit a BLA for eptinezumab early next year.

At this stage, there’s little difference among them. The four therapies have shown similar efficacy and safety in the clinic. The three marketed ones have the same wholesale acquisition cost (WAC) of $6,900 per year, which the Institute for Clinical and Economic Review (ICER) determined is cost effective, assuming a net price of $5,000 to payers after discounts (see “Getting Ahead of Headache”).

“Basically we know they work, they work quickly, and they have minimal side effects.”

Stephen Silberstein, Thomas Jefferson University

To make the strongest case possible to payers, Lilly and Amgen are gearing up to collect postmarket performance data. But those won’t be available in initial payer discussions.

Harvard Pilgrim Health Care Inc. CMO Michael Sherman told BioCentury payers are likely going to demand discounts, even though the products are considered reasonably priced by ICER. That suggests discount size will dictate formulary status, with one or more products being preferred and the others having additional pre-authorization requirements or being excluded.

Another possibility is that if all the products get some level of market access, feedback from patients and doctors could steer the market in the short term, prompting payers to prefer the one or two therapies that become most popular. For example, patients could be attracted to the less frequent dosing of Ajovy, or the greater ease of administration of Aimovig and Emgality.

Anybody’s game

Doctors who spoke to BioCentury didn’t think the data collected to date set any of the anti-CGRP agents apart.

Phase III studies of all four agents used reduction in migraine or headache frequency as the primary endpoint. Compared with placebo, the mAbs reduced mean monthly migraine days by 0.7-2.0 in episodic patients and by 1.7-2.6 in chronic patients (see “Table: CGRP Comps in Episodic Migraine”; “Table: CGRP Comps in Chronic Migraine”).

Table: CGRP comps in episodic migraine

Efficacy outcomes for mAbs that target calcitonin gene-related peptide (CGRP) or its receptor have not revealed major differences in their ability to prevent episodic migraine. Though determined at different time intervals, each reduced the number of monthly migraine days by about one or two more than placebo.

Emgality galcanezumab from Eli Lilly and Co. (NYSE:LLY) displayed the highest reduction in monthly migraine days vs. placebo, the primary endpoint in all of the trials. Aimovig erenumab-aooe from Amgen Inc. (NASDAQ:AMGN) and Ajovy fremanezumab-vfrm from Teva Pharmaceutical Industries Ltd. (NYSE:TEVA; Tel Aviv:TEVA) produced intermediate lowering of the endpoint, while eptinezumab from Alder Biopharmaceuticals Inc. (NASDAQ:ALDR) came in on the low end, yielding about one fewer migraine days. Three doctors who spoke to BioCentury did not think the efficacy differences were meaningful.

Eptinezumab is administered IV; the three other mAbs are given subcutaneously. Dosing interval...

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